Intraocular implants and methods and kits therefor

ABSTRACT

Devices, methods and kits are described for reducing intraocular pressure. The devices include a support that is implantable within Schlemm&#39;s canal and maintains the patency of the canal without substantially interfering with transmural fluid flow across the canal. The devices utilize the natural drainage process of the eye and can be implanted with minimal trauma to the eye. Kits include a support and an introducer for implanting the support within Schlemm&#39;s canal. Methods include implanting a support within Schlemm&#39;s canal, wherein the support is capable of maintaining the patency of the canal without substantial interference with transmural fluid flow across the canal.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/340,911, filed on Nov. 1, 2016, which is a continuation of U.S.patent application Ser. No. 13/445,816, filed on Apr. 12, 2012 (now U.S.Pat. No. 9,486,361), which is a continuation of U.S. patent applicationSer. No. 12/695,053, filed on Jan. 27, 2010 (now U.S. Pat. No.8,287,482), which is a continuation of U.S. patent application Ser. No.11/475,523, filed on Jun. 26, 2006 (now U.S. Pat. No. 7,909,789), thedisclosures of which are hereby incorporated by reference in theirentirety.

FIELD

The devices, kits and methods described herein relate generally tointraocular pressure reduction. More particularly, the devices, kits andmethods relate to intraocular implants implantable into Schlemm's canalthat can reduce intraocular pressure without substantially interferingwith fluid flow across Schlemm's canal.

BACKGROUND

Glaucoma is a potentially blinding disease that affects over 60 millionpeople worldwide, or about 1-2% of the population. Typically, glaucomais characterized by elevated intraocular pressure. Increased pressure inthe eye can cause damage to the optic nerve which can lead to loss ofvision if left untreated. Consistent reduction of intraocular pressurecan slow down or stop progressive loss of vision associated withglaucoma. In addition, patients are often diagnosed with pre-glaucomaand ocular hypertension when they exhibit symptoms likely to lead toglaucoma, such as somewhat elevated intraocular pressure, but do not yetshow indications of optic nerve damage. Treatments for glaucoma,pre-glaucoma and ocular hypertension primarily seek to reduceintraocular pressure.

Increased intraocular pressure is caused by sub-optimal efflux ordrainage of fluid (aqueous humor) from the eye. Aqueous humor or fluidis a clear, colorless fluid that is continuously replenished in the eye.Aqueous humor is produced by the ciliary body, and then flows outprimarily through the eye's trabecular meshwork. The trabecular meshworkextends circumferentially around the eye at the anterior chamber angle,or drainage angle, which is formed at the intersection between theperipheral iris or iris root, the anterior sclera or scleral spur andthe peripheral cornea. The trabecular meshwork feeds outwardly intoSchlemm's canal, a narrow circumferential passageway generallysurrounding the exterior border of the trabecular meshwork. Positionedaround and radially extending from Schlemm's canal are aqueous veins orcollector channels that receive drained fluid. The net drainage orefflux of aqueous humor can be reduced as a result of decreased facilityof outflow, decreased outflow through the trabecular meshwork and canalof Schlemm drainage apparatus, increased episcleral venous pressure, orpossibly, increased production of aqueous humor. Flow out of the eye canbe restricted by blockages or constriction in the trabecular meshworkand/or Schlemm's canal.

Glaucoma, pre-glaucoma and ocular hypertension currently can be treatedby reducing intraocular pressure using one or more modalities, includingmedication, incisional surgery, laser surgery, cryosurgery, and otherforms of surgery. In the United States, medications or medical therapyare typically the first lines of therapy. If medical therapy is notsufficiently effective, more invasive surgical treatments may be used.In other countries, such as those with socialized medical systems orwith nationalized health care systems, surgery may be the first line oftherapy if it is considered a more cost effective treatment.

A standard incisional surgical procedure to reduce intraocular pressureis trabeculectomy, or filtration surgery. This procedure involvescreating a new drainage site for aqueous humor. Instead of naturallydraining through the trabecular meshwork, a new drainage pathway iscreated by removing a portion of sclera and trabecular meshwork at thedrainage angle. This creates an opening or passage between the anteriorchamber and the subconjunctival space that is drained by conjunctivalblood vessels and lymphatics. The new opening may be covered with scleraand/or conjunctiva to create a new reservoir called a bleb into whichaqueous humor can drain. However, trabeculectomy carries both long andshort term risks. These risks include blockage of the surgically-createdopening through scarring or other mechanisms, hypotony or abnormally lowintraocular pressure, expulsive hemorrhage, hyphema, intraocularinfection or endophthalmitis, shallow anterior chamber angle, andothers. Alternatives to trabeculectomy are actively being sought.

Bypass stents are also used to bridge a blocked trabecular meshwork.Stents can be inserted between the anterior chamber of the eye andSchlemm's canal, bypassing the trabecular meshwork. However, it isdifficult to consistently and reliably implant a bypass stent from theanterior chamber into Schlemm's canal. The implant procedure ischallenging and stents can become clogged and lose functionality overtime. Others have inserted tubular elongated cylindrical hollow stentslongitudinally into Schlemm's canal. Cylindrical hollow stents can beconfigured to allow circumferential fluid flow around the canal. Thesetoo can lose functionality over time as a result of occlusion orscarring.

Schlemm's canal is small, approximately 190-370 microns incross-sectional diameter, and circular. Therefore, it can be difficultor expensive to design and manufacture hollow tubular stents ofappropriate dimensions for use in opening Schlemm's canal. In addition,hollow tubular stents can be prone to failure and collapse or occlusionover time, as has been shown for cardiovascular stents. Hollow tubularstents incorporating thin walls are especially prone to failure.Further, the walls of tubular stents placed lengthwise along Schlemm'scanal can have significant surface area contact with the trabecularmeshwork and/or the collector channels, which can result in blockage ofthe meshwork or collector channels, substantially interfering withtransmural flow across Schlemm's canal and into the eye's collectorchannels.

Therefore, easily manufacturable, minimally invasive devices foreffective, long-term reduction in intraocular pressure are desirable. Inaddition, methods and kits incorporating such devices are desirable.

SUMMARY

Described here are devices, kits and methods for reducing intraocularpressure. The devices for reducing pressure within the eye comprise asupport implantable circumferentially within Schlemm's canal that isconfigured to maintain the patency of at least a portion of the canal.The support occupies at least a portion of a central core of Schlemm'scanal. The support does not substantially interfere with transmural flowacross Schlemm's canal, and thereby utilizes the eye's natural drainagepathways. The support can be implanted into Schlemm's canal with minimaltrauma to the eye.

The support generally comprises a biocompatible material. At least aportion of the support can be made from a biocompatible polymer, e.g.,acrylics, silicones, polymethylmethacrylate, or a hydrogel. In addition,at least part of the support can be made from a biocompatible metal suchas gold. In some variations, at least a portion of the support is madefrom a shape memory material. Suitable shape memory materials includeshape memory polymers or shape memory alloys, such as nickel titaniumalloys. If a shape memory material is used, the support can have acompressed state prior to and during implantation into Schlemm's canal,and an expanded state following implantation to open the canal.

In some variations, the support is at least partially made from abiocompatible, biodegradable polymer. The biodegradable polymer can becollagen, a collagen derivative, a poly(lactide); a poly(glycolide); apoly(lactide-co-glycolide); a poly(lactic acid); a poly(glycolic acid);a poly(lactic acid-co-glycolic acid); a poly(lactide)/poly(ethyleneglycol) copolymer; a poly(glycolide)/poly(ethylene glycol) copolymer; apoly(lactide-co-glycolide)/poly(ethylene glycol) copolymer; apoly(lactic acid)/poly(ethylene glycol) copolymer; a poly(glycolicacid)/poly(ethylene glycol) copolymer; a poly(lactic acid-co-glycolicacid)/poly(ethylene glycol) copolymer; a poly(caprolactone); apoly(caprolactone)/poly(ethylene glycol) copolymer; a polyorthoester; apoly(phosphazene); a poly(hydroxybutyrate) or a copolymer including apoly(hydroxybutyrate); a poly(lactide-co-caprolactone); a polycarbonate;a poly(esteramide); a polyanhydride; a poly(dioxanone); a poly(alkylenealkylate); a copolymer of polyethylene glycol and a polyorthoester; abiodegradable polyurethane; a poly(amino acid); a polyetherester; apolyacetal; a polycyanoacrylate; a poly(oxyethylene)/poly(oxypropylene)copolymer; and blends and copolymers thereof.

The support can comprise an active agent. For example, a support can becoated or impregnated with an active agent. Alternatively, an activeagent can be dispersed within the support, e.g., by filling a cavitywithin the support. The active agent can include a prostaglandin, aprostaglandin analog, a beta blocker, an alpha-2 agonist, a calciumchannel blocker, a carbonic anhydrase inhibitor, a growth factor, ananti-metabolite, a chemotherapeutic agent, a steroid, an antagonist of agrowth factor, or combinations thereof. The release of the active agentcan be controlled using a time release system, e.g., by embedding orencapsulating the active agent with a time release composition.

In some variations, the support will be solid. In other variations, atleast a portion of the support will be hollow or porous. The surface ofthe support may be smooth, rough, spiked, or fluted. In still othervariations, at least part of the support will be made from mesh. Thesupport can include at least one fenestration and one or more rod-likemembers.

In some variations, the support comprises at least two adjacent beads.Adjacent beads can have the same or different sizes and shapes, and canbe made from the same or different materials. The bead shapes can bespherical, spheroid, ovoid, cylindrical, cuboid, cubical, conical,discoid, helical, or segments thereof. In some variations, there is aconnector linking at least two adjacent beads together. If there is aconnector, it can be rigid or flexible. If there is more than oneconnector, e.g., two connectors inserted between three beads, theconnectors may be of the same or different lengths. The connectors caninclude the same or different material as the beads they connect. Aconnector can also function as a spacer configured to provide spacebetween adjacent beads. In some variations, the support comprises atleast two discs separated by, and connected with, a connector. The discsmay include fenestrations. The connector may also comprise a guide wireover which a fenestrated bead can be threaded into the canal of Schlemm.

The support can extend approximately all the way around Schlemm's canal,if the support has a circumference approximately equal to thecircumference of Schlemm's canal. Alternatively, the support can extendonly about half way around the circumference of Schlemm's canal, orabout a quarter way around the canal. In some variations, the supportwill extend less than a quarter circumference of Schlemm's canal. Thesupport can be configured to contact the inner surface of the wall ofSchlemm's canal at two, three or more points. In some variations, thesupport can be attached to tissue. The support may comprise a stiffarcuate member having a radius of curvature smaller or larger than thatof Schlemm's canal.

In some variations, the support can be altered using electromagneticradiation. For example, a laser having a wavelength absorbable by atleast one localized portion of the support can be used to alter thesupport. In other variations, electromagnetic radiation can be used torelease an active agent from the support. In still other variations, thesupport can be visually enhanced using fluorescence or phosphorescenceemission. For example, the support can comprise a chromophore thatfluoresces or phosphoresces upon excitation with a light source. In somevariations, the emitted fluorescence or phosphorescence is in thewavelength range of about 300 nm to about 800 nm. In some variations,the support can comprise a chromophore that enhances postoperativemonitoring of the support.

Kits for reducing intraocular pressure are also provided. The kitscontain a support that can be implanted circumferentially withinSchlemm's canal. The support is configured to maintain the patency of atleast part of Schlemm's canal. The support occupies at least a portionof a central core of Schlemm's canal and does not substantiallyinterfere with transmural flow across the canal. The kits also containan introducer for implanting the support within the canal. In somevariations, the kits include a positioning device for adjusting thesupport within the canal. In other variations, kits includeinstructions. In still other variations, the kits include an activeagent. Some kits contain at least two supports. If more than one supportis included, the kits can include at least two introducers fordelivering the supports. Multiple supports within the same kit can havethe same or different shape, size, or composition. Multiple supportswithin the same kit can be connected together or remain separate. Insome variations, kits include a fixation device for attaching a supportto tissue. In other variations, kits may include a system for visuallyenhancing the appearance of the support.

Methods for reducing intraocular pressure are also described. Themethods include inserting a support circumferentially within Schlemm'scanal. The support is configured to maintain the patency of at leastpart of the canal. The support occupies at least a portion of a centralcore of Schlemm's canal, and does not substantially interfere withtransmural flow across the canal. In some variations, the methods alsoinclude dilating Schlemm's canal prior to insertion of the support. Instill other variations, the methods comprise anchoring the support totissue. The methods can include implanting at least two supports. Ifmore than one support is implanted within a single eye, the multiplesupports can be positioned circumferentially adjacent to each other orcircumferentially opposed (i.e., positioned about 180° apart) to eachother within Schlemm's canal. Multiple supports within one eye can beconnected or remain separate. In some variations of the methods, thesupport is illuminated with a light source to visually enhance theposition of the support. In other variations of the methods, the supportcan be altered using electromagnetic radiation. For example, a laserabsorbed by at least one localized portion of the support can be used toalter the support. The alteration can comprise the creation orenlargement of an aperture in the support. If electromagnetic radiationis used to alter a support, the alteration can occur before implantationor after implantation.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 provides a partial cross-sectional side view of a normal humaneye.

FIG. 2 provides a partial cross-sectional side view of a normal drainagepath of fluid from the eye.

FIG. 3 shows a front view of normal fluid drainage from the eye.

FIG. 4A shows an alternative front view of normal fluid drainage pathsfrom the eye. FIG. 4B shows a cross-sectional view along line I-I′.

FIG. 5A provides a front view of an eye in which Schlemm's canal isnarrowed or collapsed. FIG. 5B shows a front view of a device includinga support inserted into Schlemm's canal that allows transmural flowacross the canal. FIG. 5C illustrates an alternate design for a deviceinserted into Schlemm's canal that allows transmural flow across thecanal.

FIG. 6A shows side views of various element or bead configurations thatcan be used in the supports described herein. FIG. 6B shows thecorresponding front views of the element or bead configurations shown inFIG. 6A. FIG. 6C illustrates an element or bead having fenestrations.

FIG. 7A illustrates a support having multiple juxtaposed beads. FIG. 7Billustrates a support having multiple juxtaposed and connected beads.FIG. 7C shows an alternate configuration of a support having multiplejuxtaposed and connected beads. FIG. 7D shows a support having multiple,spaced-apart but connected beads. FIG. 7E illustrates beads threadedonto a connector.

FIGS. 8A-B show side and front views, respectively, of a support havingan open network structure. FIGS. 8C-D show side and front views,respectively, of a support having a longitudinal zig-zag configurationthat will contact the wall of Schlemm's canal at at least three points(labeled P₁, P₂, P₃). FIGS. 8E-F show side and front views,respectively, of a support having a rod-like member with continuouslyfluted edges and fenestrations. FIGS. 8G-H show side and front views,respectively, of another variation of a support having a rod-like memberwith continuously fluted edges.

FIGS. 9A-B show expanded cross-sectional views of a support implantedwithin Schlemm's canal.

FIGS. 10A-C illustrate various configurations of supports implanted intoSchlemm's canal.

FIGS. 11A-B illustrate two configurations of supports having a smallerradius of curvature than Schlemm's canal. FIG. 11C shows a supporthaving a larger radius of curvature than Schlemm's canal.

FIG. 12A illustrates a variation of a support traversing the center ofthe central core of Schlemm's canal. FIG. 12B shows a cross-sectionalview along line II-II′. FIG. 12C illustrates a variation of a supporttraversing the central core of the canal. FIG. 12D shows across-sectional view along line III-III′. FIG. 12E illustrates avariation of a support that occupies the majority of the central core ofthe canal. FIG. 12F shows a cross-sectional view along line IV-IV′. FIG.12G illustrates a variation of support having an open network thatoccupies a portion of the central core of the canal. FIG. 12H shows across-sectional view along line V-V′.

FIG. 13 shows an illustrative example of a support that can be modifiedusing electromagnetic radiation.

FIG. 14A illustrates a syringe that can be used to insert a support intoSchlemm's canal.

FIG. 14B illustrates a variation in which a support is threaded onto aguide element for insertion and positioning in Schlemm's canal. FIG. 14Cillustrates a cross-sectional view of a support having a central bore toaccommodate a guide element. FIG. 14D illustrates a variation in which asyringe and a guide element are used for insertion and positioning of asupport in Schlemm's canal.

DETAILED DESCRIPTION

Described here are devices, kits and methods to reduce intraocularpressure by maintaining or restoring Schlemm's canal so that at least aportion of the canal is patent or unobstructed. The devices, kits andmethods operate to keep Schlemm's canal from collapsing while notsubstantially interfering with the eye's natural drainage mechanism foraqueous humor, in which transmural fluid flow across Schlemm's canaloccurs. The devices are implantable in Schlemm's canal with minimaltrauma to the eye.

With reference to the figures, FIG. 1 shows a partial cross-sectionalview of the anatomy of a normal human eye. Ciliary body 12 is connectedto iris 18 and to lens 16 via zonular fibrils 14. The anterior chamberof the eye 20 is bounded on its anterior (front) surface by cornea 24.In the center of iris 18 is pupil 22. Cornea 24 is connected on itsperiphery to sclera 26, which is a tough fibrous tissue forming thewhite shell of the eye. Trabecular meshwork 28 is located on the outerperipheral surface of anterior chamber 20. The trabecular meshworkextends 360° circumferentially around the anterior chamber. Located onthe outer peripheral surface of meshwork 28 is Schlemm's canal 30.Schlemm's canal extends 360° circumferentially around the trabecularmeshwork. At the apex formed between iris 18, meshwork 28 and sclera 26is angle 32. Conjunctiva 34 is a membrane overlaying sclera 26 andlining the inside of the eyelid (not shown).

FIG. 2 shows a partial cross-sectional view of flow of aqueous humorwithin and out of a normally functioning human eye. Aqueous humor isproduced in ciliary body 12 and its path through and out of the eye isindicated by solid directional line 36. The aqueous humor flows fromciliary body 12, between lens 16 and iris 18, through pupil 22 intoanterior chamber 20, across trabecular meshwork 28, across Schlemm'scanal 30, into aqueous veins or collector channels (not shown) andfinally into the bloodstream via conjunctival vasculature.

FIG. 3 shows a front view of normal flow of aqueous humor out of theeye. Aqueous humor enters anterior chamber 20 via pupil 22. The fluidflows outwardly toward the periphery of the eye, with the general pathof flow indicated by solid directional lines 36. The fluid crossestrabecular meshwork 28 and traverses Schlemm's canal 30 to reach aqueousveins or collector channels 38. There are typically 25-30 collectorchannels located in a human eye. Collector channels 38 are connected tovasculature 40, whereby the drained aqueous humor enters thebloodstream. Although the direction of net or bulk fluid flow isdepicted as radially outward by directional lines 36 from pupil 22 forsimplicity, actual fluid flow in an eye may follow more varied paths.

Different fluid flow paths in and across Schlemm's canal are illustratedin FIGS. 4A-B. FIG. 4A shows a front view of an eye, and FIG. 4B showsan expanded cross-sectional view along line I-I′. Circumferential (i.e.,longitudinal) flow along and around circular canal 30 is depicted bydirectional lines 50. Fluid that does not traverse canal 30 to reachcollector channels 38 may not be effectively drained from the eye.Examples of fluid flow paths that can effectively drain the eye areillustrated by directional lines 52, 52′, and 52″. In each of thesepaths, fluid enters trabecular meshwork 28 along its inner peripheralsurface 60 and exits the meshwork along its outer peripheral surface62′. Meshwork outer peripheral surface 62′ provides the inner peripheralsurface or wall of Schlemm's canal 30. Transmural fluid flow acrossSchlemm's canal involves two instances of transmural flow across wallsor boundaries. First, fluid must flow from trabecular meshwork 38through inner peripheral surface or wall 62′ of Schlemm's canal 30 toreach lumen 64 of the canal. Second, fluid must flow from lumen 64through canal outer peripheral wall 62″ through apertures 38′ to entercollector channels 38. Finally, the collector channels 38 feed thedrained fluid into vasculature. Lumen 64 of canal 30 includes a centralcore region 67. Thus, fluid flow from the eye differs from fluid flow inother vessels in the body where fluid need only flow longitudinallyalong the vessel, such as blood flowing through a vein.

Devices

Devices to reduce intraocular pressure comprising a support that can beimplanted circumferentially in Schlemm's canal to maintain the patencyof at least a portion of the canal are described here. The supportoccupies at least a portion of a central core of Schlemm's canal anddoes not substantially interfere with transmural flow across the canal.By “maintain the patency” of at least a portion the canal, it is meantthat the support operates to keep the canal at least partiallyunobstructed to transmural flow, such that fluid can 1) exit through thetrabecular meshwork; 2) traverse the canal; and 3) drain via thecollector channels. To maintain the patency of the canal, it is notnecessary that the support leave the canal unobstructed in regard tocircumferential flow. By “does not substantially interfere” withtransmural flow, it is meant that the support does not significantlyblock either fluid outflow from the trabecular meshwork or fluid outflowto the collector channels. In many variations, the support allowsbetween about 0.1 and about 5 microliters per minute aqueous outfluxfrom the eye through the trabecular meshwork and collector channels. The“central core of Schlemm's canal” refers to the region around thecross-sectional center of the canal in the interior space of the canallumen, i.e., not on the periphery of the canal. Therefore, a device thatoccupies at least a portion of a central core of Schlemm's canal cantraverse at least a portion of the canal's lumen.

Therefore, devices described here need not comprise an open-endedtubular support placed longitudinally along Schlemm's canal, i.e., thedevices and supports can be non-tubular. A longitudinal, open-endedtubular support can enable longitudinal flow along the canal. However,even if fluid can flow longitudinally (i.e., circumferentially) alongSchlemm's canal, the eye may not be effectively drained unless the fluideventually traverses the canal. That is, transmural fluid flow acrosstwo boundaries must occur: 1) fluid must flow from the trabecularmeshwork through a canal inner wall coincident with an outer peripheralboundary of the trabecular meshwork to reach the canal lumen; and 2)fluid must flow from the canal lumen through apertures in the canalouter peripheral wall to reach the connector channels. The collectorchannels are then able to further disperse the fluid and complete thenatural draining process. A tubular support inserted longitudinally intothe canal can have significant surface area overlap with surfaces of thecanal such that transmural flow across the canal may be significantlyimpeded. A longitudinal tubular support placed in Schlemm's canal mayblock flow into the canal from the trabecular meshwork and block flowout of the canal into the collector channels.

Devices described herein for treating elevated intraocular pressureinclude a support that is implanted within Schlemm's canal. In manyinstances, the device will reduce the intraocular pressure by 1-40 mmHg, for example by at least 2 mm Hg. In other instances, the device willreduce intraocular pressure by at least 4 mm Hg, or at least 6 mm Hg, orat least 10 or 20 mm Hg. In still other instances, the device willoperate to bring the intraocular pressure into the range of about 8 toabout 22 mm Hg. The support can be configured in a variety of ways to atleast partially prop open Schlemm's canal thereby maintaining itspatency without substantially interfering with or impeding transmuralfluid flow across Schlemm's canal. In some variations, the support mayinterfere with or block longitudinal flow along or around the canal. Inmany instances, the support will be contained entirely within Schlemm'scanal. In some variations the support will be implanted within thecanal, but may extend partially beyond Schlemm's canal, e.g., into thetrabecular meshwork.

In some variations, a support to maintain at least partial patency forSchlemm's canal to enable fluid flow between an inner wall of the canaland an outer wall of the canal can comprise elements or structures suchas bead-like elements or beads, which can be connected together, e.g.,as a string of beads. Individual elements or beads or a connected groupof elements or beads can be inserted directly into Schlemm's canal. Amore detailed description of supports incorporating elements or beads isprovided below.

FIG. 5A illustrates a front view of an eye having a narrowed orcollapsed Schlemm's canal 30, where canal outer peripheral wall 62″ isvery close to canal inner peripheral wall 62′. Although Schlemm's canal30 is depicted in FIG. 5A as being uniformly narrow around the entirecircumference of canal, it is possible that only a portion of Schlemm'scanal is narrowed or collapsed. When Schlemm's canal is collapsed ornarrowed, net efflux of aqueous from the anterior chamber to thecollector channels 38 is diminished, thereby increasing intraocularpressure. As a result, the risk of pre-glaucoma, ocular hypertension, orglaucoma can increase.

FIG. 5B illustrates an example of a device 70 inserted into Schlemm'scanal 30 through incision site 74. Device 70 in this example ispositioned to one side of incision site 74. Device 70 includes support72 that is configured to keep Schlemm's canal at least partially open totransmural fluid flow across both canal inner wall 62′ and canal outerwall 62″ to reach collector channels 38 via apertures 38′. In theexample shown in FIG. 5B, support 72 includes elements or beads 76connected with connectors 78. In this variation, the distance betweencanal inner wall 62′ and outer wall 62″ is approximately determined bythe cross-sectional dimension of support 72, which is in turn determinedby the largest cross-sectional diameter of the beads 76. Therefore,circumferential (i.e., longitudinal) fluid flow around and along thecanal 30 indicated by directional line 50 may be inhibited by theinsertion of support 72 into the canal. However, transmural flow acrossboth walls or boundaries of the canal indicated by directional lines 52,52′, 52″ is enhanced by support 72 and fluid is able to reach collectorchannels 38 and be drained from the eye. As a result, support 72 caneffectively reduce intraocular pressure by utilizing the eye's naturaldrainage mechanism. Incision 74 need only be large enough to accommodatethe diameter of beads 76, so that trauma to the eye is minimized. Beadscan have cross-sectional dimensions in the range from about 50 micronsto about 500 microns. Insertion of beads having relatively smallcross-sectional diameters (e.g., about 50 microns) into Schlemm's canalopen the canal less than the normal cross-sectional diameter of thecanal, which is about 190 to about 370 microns, but still can maintainthe patency of the canal. Insertion of beads having relatively largecross-sectional diameters (e.g., greater than about 300 microns) canopen the canal as large as or larger than the canal's normalcross-sectional diameter and also can operate to stretch the trabecularmeshwork. Stretching the trabecular meshwork may further enhancedrainage.

FIG. 5C illustrates an alternate configuration of a device 80 insertedinto Schlemm's canal 30 through incision site 84. Device 80 includessupport 82 that extends to both sides of incision site 84. Support 82includes elements or beads 76 connected with connectors 88 and 88′. Inthis example, connector 88′ is of a different length than connectors 88.As in FIG. 5B, beads 76 may impede circumferential (i.e., longitudinal)fluid flow around and along canal 30 indicated by directional line 50.However transmural flow across the canal is enhanced by support 82 thatmaintains patency across the canal and allows fluid to reach collectorchannels 38. If the beads are fenestrated or comprise rough, spiked, orfluted perimeters, then circumferential fluid flow through or around thebeads may also occur.

Elements or beads used in a support may be hollow and closed structures,open structures, solid structures, porous structures, or any combinationthereof, and may be of any suitable shape. FIGS. 6A and 6B illustrateside and front views, respectively, of exemplary elements or beads thatmay be used in the supports described here. As shown, solid 90 or hollow91, spherical 90, spheroid 92, ovoid 93, conical 94, disk-shaped 95,polyhedral 96, rod-like 97, or beads with fluted edges 98, rough edges,89, or spiked edges 88 may be used. In some instances, it may be desiredto round corners or edges of the beads. As illustrated in FIG. 6C,elements or beads 76 may include fenestrations 99, 99′. Fenestrationsmay have any suitable cross-sectional shape, such as round orquadrilateral. Although a disc-shaped bead 76 is shown in FIG. 6C, anyshape of bead can be fenestrated.

As illustrated in the variations shown in FIGS. 7A-E, two or more beads76 in a support may be adjacent to each other. Adjacent beads may bejuxtaposed (FIG. 7A), connected and juxtaposed (FIGS. 7B and 7C), orconnected together with connectors 100, 100′ to form intervals betweenbeads (FIG. 7D). In addition, beads may be threaded onto a connector 101(FIG. 7E). Multiple beads used in a single support may have the same ordifferent shapes, and may be made of the same or different materials.

Junctions 102 between beads as shown in FIG. 7B can be made using anysuitable technique, such as by using an adhesive, chemical bonding,mechanical interlocking, or welding. Beads may also be juxtaposed andconnected as shown in FIG. 7C by threading onto a guide element 104.Guide element 104 can comprise a fiber, a suture, a guide wire, afixture, or the like. The beads can be fixed in a juxtaposedconfiguration on a guide element, e.g., by knotting ends of the fiber orby providing other end-blocking devices 106, such as clips, caps,protrusions, or the like on ends 108 of element 104. Any or all of thebeads can be attached to guide element 104, e.g., beads occupying endpositions may be attached to element 104 and function as blocking beadsto keep beads from sliding off ends 108 of element 104. Alternatively,beads may slide along element 104. Guide element 104 can be flexible,such as thin polymer threads, such as a suture, or metal wires.Alternatively, element 104 can be flexible but fixable, such as one ormore shapeable metal wires that can be bent into a desired position andmaintain that position against some amount of external stress orpressure. In other variations, guide element 104 can be rigid, e.g., amolded polymeric piece or a stiff metal piece.

As shown in FIG. 7D, multiple connectors 100, 100′ may be used in asingle support, with at least one connector inserted between adjacentbeads 76. If multiple connectors are used, they may be of the same ordifferent lengths. In addition, multiple connectors within the samesupport may be made of the same or different materials, and theconnectors may be made of the same or different materials than thebeads. Discrete connectors 100, 100′ can be inserted between beads 76and attached to adjacent beads using any suitable method including usingadhesives, chemical bonding, welding, mechanical interlocking, knots, orany combination thereof. In some variations, connectors 100, 100′between beads can be configured to function as spacers betweenindividual beads. As illustrated in FIG. 7E, beads 76 can also bethreaded onto a connector 101. If the beads are threaded onto aconnector, the beads can be maintained in fixed positions along theconnector 101 by any suitable method, including using adhesives,chemical bonding, welding, clips, protrusions on the connector,mechanical interlocking locking between a connector and a bead, knots,or any combination thereof. Alternatively, some or all beads may slidealong connector 101. Connectors 100, 100′, 101 can be flexible, such asthin polymer threads or metal wires. Connectors 100, 100′, 101 can alsobe flexible but fixable, such as shapeable metal wires. Alternatively,connectors 100, 100′, 101 may be rigid, such as molded polymericconnectors or stiff metal connectors.

Supports of the devices described here need not contain beads. Forexample, a support can be a unitary structure of fixed or variablelength. Supports can be solid, hollow, or porous, or any combinationthereof. For example, a support can be partially solid and partiallyhollow. Examples of support configurations are shown in side view andfront view in FIGS. 8A-F. As illustrated in FIG. 8A-B, a support canhave an open network structure. Such a support can be fabricated out ofshapeable metal wires, for example. The support illustrated in FIGS.8A-B will have minimal surface area contact with the walls of Schlemm'scanal, i.e., only point contacts at the end of wires or fibers 170.Alternatively, a support having an open network structure can be atleast partially made from a mesh or foam. The mesh or foam can be madeof any suitable material, e.g., metal or plastic. As shown in FIGS.8C-D, the support can have a sinusoidal or zig-zag configurationextending along a selected length of Schlemm's canal. For the exampleshown in FIG. 8C, the support will contact the wall of Schlemm's canalat at least three points, labeled P₁, P₂, and P₃, after implantation. InFIGS. 8E-H, examples of rod-like supports having fluted edges are shown.In FIGS. 8E-F, fluted edges 110 extend longitudinally along sides 112between ends 114 of the support to form structures 116. Structures 116can include fenestrations 113. The support can include central bore 117.In FIGS. 8G-H, fluted edges 110′ extend along sides 112′ to formstructures 116′. Structures 116′ have serrated outer surfaces 115′extending between ends 114′. The support can include central bore 117′.In the variations illustrated in FIGS. 8E-H, the support may contact thecanal walls at at least four points. In some variations, the support isadjustable.

A common characteristic of the support configurations described here isthat they need not have continuous or extensive contact with a wall ofSchlemm's canal. Indeed, many of the described devices and structureshave minimal tangential, periodic, or sporadic contact with the wall.The surface of the support can be rough, smooth, spiked or fluted. Asthe example shown in FIGS. 8A-B shows, some supports only have pointcontacts with the canal wall. For the supports shown in FIGS. 5B-C, therounded beads of each of the supports make only tangential contact withthe canal wall. Bead shapes can be selected or designed to have minimalsurface area contact with canal walls, e.g., beads 98 having flutededges as shown in FIGS. 6A-B may have low surface area contact withcanal walls. In addition, supports having widely spaced apart beads,e.g., by connectors illustrated in FIGS. 7D-E that can function to spacebeads at desired intervals to reduce contact with canal walls yetoperate to keep the canal open. As illustrated above with respect toFIGS. 8C-D, in some variations, the support contacts the interior wallof the canal at at least two points; or at at least three points.

Expanded cross-sectional views of a support 152 implantedcircumferentially in Schlemm's canal are provided FIGS. 9A-B. Thefraction of canal wall surface area in contact with a support can beestimated by viewing the inside of Schlemm's canal as a slightly arcuatecylinder C having length L, extending circumferentially from a first endX₁ to a second end X₂ of support 152, and inside radius R_(i). In somevariations, the support contacts less than 0.1% or less than 1% of thesurface area of the cylinder C as described above. In other variations,the support contacts less than 10% of the surface area of C. In stillother variations, the support contacts less than 30% of the surface areaof C. For example, the support 152 shown in FIGS. 9A-B contacts thecanal wall 62 only at bead outer peripheral edges at E₁-E₇, along adistance of the bead width B_(W). There is no contact with the canalwalls where connectors 156 space apart beads 154, and no contact influted regions 160 of beads 154. The design feature of minimal supportcontact with canal walls allows a support to maintain patency of thecanal without substantially interfering with transmural flow across thecanal. If a substantial portion of the surface area of the innerperiphery of the canal adjacent to the trabecular network or of thesurface area of the outer periphery of the canal where the collectorchannels are located is blocked, effective fluid flow across the canalmay be impaired.

Supports can have variable lengths and thicknesses. For example, thelength of supports using beads can be tuned by varying the number, type,or spacing of beads, or any combination thereof. The thickness of asupport can be increased by adding one or more beads having largerdimensions. Unitary supports can also be built with varying lengths, orwith adjustable (e.g., trimmable) dimensions. For example, for a supportmade of shapeable metal having a sinusoidal or zig-zag configuration asshown FIGS. 8C-D, a cross-sectional dimension 117 of the support can bedecreased or increased by apply tension along dimension 119. Asillustrated in FIG. 10A, a support 160 can extend essentially around theentire circumference of Schlemm's canal 30. Alternatively, a support canextend approximately half way around the circumference of the canal (notshown). As shown in FIG. 10B, a support 162 can extend less than halfway around the canal. As shown in FIG. 10C, a support 164 can extend aquarter or less of the circumference around the canal. In addition, morethan one support 164, 166, 168 can be inserted into a single Schlemm'scanal. If multiple supports are inserted into a single canal, they canbe of different shapes, lengths, materials or sizes.

A support can be configured such that it will open the canal beyond amaximum cross-sectional dimension of the support itself. For example, asillustrated in FIG. 11A, device 130 comprising support 132 is insertedinto Schlemm's canal 30. Support 132 comprises beads 134 which have amaximum cross-sectional dimension B_(D). Support 132 comprises a stiffarcuate element 135 with a radius of curvature R_(supp) smaller than theradius of curvature of Schlemm's canal R_(SC). The smaller, fixed radiusof curvature R_(supp) of arcuate member135 urges canal 30 to open morethan B_(D). In another variation shown in FIG. 11B, support 179comprises an arcuate member 180 without beads having a radius ofcurvature R_(supp) that is less than the radius of curvature R_(SC) ofthe canal. Member 180 is sufficiently stiff to urge the canal open. Inanother variation shown in FIG. 11C, support 181 comprises an arcuatemember 182 having a radius of curvature R_(supp) larger than that ofSchlemm's canal R_(SC). Member 182 is also sufficiently stiff to urgethe canal open. Arcuate members 135, 180 and 182 can comprise a shapememory material such as Nitinol, for example. As indicated in FIG. 11C,support 181 can include beads 184. To urge open the canal, the radius ofcurvature R_(supp) of an arcuate members can be about 10%, 20%, 30%,40%, or 50% or smaller or larger than that of Schlemm's canal R_(SC).For example, an arcuate member can have a radius of curvature of about 3mm to about 8 mm. In some variations, the radius of curvature of anarcuate member R_(supp) in a support is about 3 mm, or about 4 mm, orabout 5 mm. In other variations, the radius of curvature R_(supp) of anarcuate member in a support is about 6 mm, or about 7 mm, or about 8 mm.

The supports described here occupy at least a portion of a central coreof Schlemm's canal. The central core of Schlemm's canal is the regionaround the cross-sectional center of the canal in the interior space ofthe canal lumen. A support that occupies at least a portion of thecentral core of the canal can traverse at least a portion of the canallumen. For example, some variations of supports can traverse thecross-sectional center of the canal at at least one point. Referring toFIG. 12A, a front view of a support 220 having beads 222 connected withconnectors 224 is provided. FIG. 12B shows an expanded cross-sectionalview along line II-II′. Support 220 occupies a portion canal centralcore 67 in canal lumen 64. Trabecular meshwork 28 is shown adjacent tocanal 30. In this variation, support 220 traverses the cross-sectionalcenter 66 of the canal. In other variations, supports can traverse thelumen of the canal off-center, e.g., appearing as a chord across thecanal lumen in cross-section. Referring to FIG. 12C, a front view of anarcuate support 210 is shown. FIG. 12D shows an expanded cross-sectionalview along line III-III′. Support 210 traverses and occupies a portionof central core 67 in lumen 64 of canal 30 without passing through canalcenter 66. In some variations, the support can occupy the majority ofthe central core of the canal. Referring to FIG. 12E, a front view ofsupport 230 comprising disc-like beads 232 is shown. A cross-sectionalview along line IV-IV′ is shown in FIG. 12F. As illustrated in FIG. 12F,bead 232 with fenestrations 234 occupies the majority of central core 67of canal 30. In other variations, the support occupies only a smallportion of the central core of the canal. For example, in FIG. 12G, afront view of a support 240 having an open network structure is shown. Across-sectional view along line V-V′ is shown in FIG. 12H.

A support can made of a variety of different materials. In general, thesupport should comprise a biocompatible material, such as abiocompatible polymer, ceramic or ceramic composite, glass or glasscomposite, metal, or combinations of these materials. Examples ofbiocompatible metals include stainless steel, gold, silver, titanium,tantalum, platinum and alloys thereof, cobalt and chromium alloys, andtitanium nickel alloys such as Nitinol. Examples of biocompatiblepolymers include high density polyethylene, polyurethane, polycarbonate,polypropylene, polymethylmethacrylate, polybutylmethacryate, polyesters,polytetrafluoroethylene, silicone, polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl chloride, ethyl vinyl acetate, collagen, collagenderivatives, flexible fused silica, polyolefins, NYLON® polymer,polyimide, polyacrylamide, fluorinated elastomers, and copolymers andblends thereof. In addition, biocompatible hydrogels can be used insupports and devices described herein. As discussed in more detailbelow, biocompatible polymers may be biodegradable. A support can bemade of a single material or a combination of materials. In somevariations, a support made from a first material is coated with a secondmaterial, e.g., to enhance or improve its biocompatibility.

In some examples, the biocompatible polymer in a support will include abiodegradable polymer. Examples of suitable biodegradable polymersinclude collagen, a collagen derivative, a poly(lactide), apoly(glycolide), a poly(lactide-co-glycolide), a poly(lactic acid), apoly(glycolic acid), a poly(lactic acid-co-glycolic acid), apoly(lactide)/poly(ethylene glycol) copolymer, apoly(glycolide)/poly(ethylene glycol) copolymer, apoly(lactide-co-glycolide)/polyethylene glycol) copolymer, a poly(lacticacid)/poly(ethylene glycol) copolymer, a poly(glycolicacid)/poly(ethylene glycol) copolymer, a poly(lactic acid-co-glycolicacid)/poly(ethylene glycol) copolymer, a poly(caprolactone), apoly(caprolactone)poly(ethylene glycol) copolymer, a polyorthoester, apoly(phosphazene), a poly(hydroxybutyrate) or a copolymer including apoly(hdroxybutyrate), a poly(lactide-co-caprolactone), a polycarbonate,a poly(esteramide), a polyanydride, a poly(dioxanone), a poly(alykylenealkylate), a copolymer of polyethylene glycol and a polyorthoester, abiodegradable polyurethane, a poly(amino acid), a polyetherester, apolyacetal, a polycyanoacrylate, a poly(oxyethylene)/poly(oxypropylene)copolymer, and blends and copolymers thereof.

At least a portion of the support can be made from a shape memorymaterial. For example, shape memory alloys, e.g. a nickel-titanium alloycan be used. In addition, shape memory polymers, e.g., polymers madefrom copolymerizing monomers oligo(e-caprolactone) dimethacrylate andn-butyl acrylate or polymers based on styrene acrylate, cyanate esterand epoxies, can be used. If a shape memory material is used in thesupport, the support can have a compressed state prior to and duringimplantation, and an expanded state following implantation. The use of acompressed state support comprising a shape memory material can allowfor a smaller incision and facilitate insertion into a narrowed orcompressed Schlemm's canal. Once implanted, the support can be expandingusing any suitable method, e.g., thermally activated by body heat or analternate heat source, to adopt an expanded state, thereby opening thecanal.

The support can include an active agent, such as a pharmaceutical.Active agents can include prostaglandins, prostaglandin analogs, betablockers, alpha-2 agonists, calcium channel blockers, carbonic anhydraseinhibitors, growth factors, such as tissue growth factors and vascularendothelial growth factors, anti-metabolites, chemotherapeutic agentssuch as mitomycin-C,5-fluorouracil, steroids, antagonists of growthfactors such as antagonists of vascular endothelial growth factors, orcombinations thereof. The active agent can be provided as a coating onat least a portion of a support. The active agent can be deliveredthroughout the eye by dissolution or other dispersal mechanisms.Alternatively, at least a portion of the support can be impregnated withthe active agent. In other embodiments, the active agent can bedispersed within at least a portion of the support. For example, acavity in the support can be filled with the active agent.

The delivery of the active agent can be controlled by time-release. Forexample, the portion of the support containing the active agent caninclude a time release coating or time release formulation designed togradually dissipate the active agent over a certain period of time.Biodegradable coatings and formulations for time-release of activeagents are known in the art. In some variations, the support cancomprise multiple layers, where the layers each comprise an activeagent. For example, support layers can be used to release a series ofdifferent agents, or a series of doses of the same agent. Such layerscan be part of a coating applied to a support, or part of a supportbody. In addition, the support can comprise biodegradable layerscontaining no active agent that can be applied or interspersed betweenother layers to further control delivery of active agents to the eye.

In some variations, it will be desirable to change or alter the supportusing electromagnetic radiation. For example, at least a portion of asupport can be fenestrated, perforated, bent, shaped or formed using alaser to enhance intraocular pressure reduction. As illustrated in FIG.13 , predetermined localized portions 120 of support 122 can be designedto absorb light of a certain wavelength or wavelength range.Preferential absorption can be achieved by material selection and/or bydoping with chromophores. Upon irradiation with sufficient energy at theselected wavelength or wavelength range, the patterned regions 120 willablate or melt, leaving new or enlarged perforations or indentations inthe support. For example, a pulsed titanium sapphire laser operatingbetween about 750 and about 800 nm can be used to ablate gold regions.If beads 126 in support 120 are hollow, then after irradiation andablation, features 120 will become fenestrations. The fenestrations canbe created to make support 122 more porous in nature or to allow releaseof an active agent from within a support, e.g., from within beads 126.Alternatively, it is possible to use a mask in combination withelectromagnetic radiation to alter a support, such as by patterning ormachining. The modification of a support using electromagnetic radiationcan be carried out prior to or subsequent to insertion.

In some variations, the visual appearance of the support can be enhancedunder certain conditions to facilitate placement or to monitor theposition or condition of the support. Visual enhancement can be achievedby incorporating into or onto the support chromophores that fluoresce orphosphoresce upon excitation with a light source. Chromophores can alsoassist a clinician in verifying the position of the supportpostoperatively using a gonioscope, for example. Light sources caninclude lasers, lamps, and light emitting diodes. In some instances,transmission or absorption filters may be used to select the wavelengthof the excitation source or to detect or view emission. Emission from asupport capable of visual enhancement may be in the wavelength range ofabout 300 nm to about 800 nm. The chromophores can be an integralcomponent of the material making up the support, doped into supportmaterial, or coated or sprayed onto the support. Visually-enhancingchromophores can be applied on a temporary basis, or on a permanentbasis. An example of a suitable chromophore is fluorescein, which can beexcited with any laser or lamp emitting at about 400 to about 500 nm. Inaddition, phosphorus-based chemiluminescent or photoluminscent pigmentscan be used, which can be selected to absorb at various wavelengthsacross the visible spectrum.

In some variations, the support may be capable of being attached totissue. For example, the support may include a hook, loop, clip,extension, or the like that may be easily attached to tissue. Thesupport may also be attached to tissue using sutures or adhesives. Thesupport may be attached to tissue using more than one attachment method,e.g., suturing may be used in combination with a loop, or an adhesivemay be used in combination with a hook. In other variations, the supportmay be allowed to self-position in Schlemm's canal. In still othervariations, the support may be mobile within Schlemm's canal.

Kits

Kits for reducing intraocular pressure are provided, where the kitscontain at least one support that can be implanted circumferentiallywithin Schlemm's canal configured to maintain the patency of at least aportion of Schlemm's canal. The support occupies at least a portion of acentral core of Schlemm's canal and does not substantially interferewith transmural flow across the canal. The kits also provide anintroducer or delivery device for implanting the support in the canal.The support and introducer are provided in packaged combination in thekits. The kits can also include instructions for use, e.g., forimplanting and inspecting the support.

The introducer can be inserted into the eye and is capable of implantingthe support at the desired implantation position within Schlemm's canal.For example, an introducer may include a tubular cannula through whichthe support may be passed. In addition to a cannula, the introducer mayinclude a tubular or solid pusher rod that can be used to push oradvance the support into and/or around Schlemm's canal. Alternatively, apusher rod or plunger can be used without a cannula to introduce asupport into the canal. A support can be installed into the lumen of acannula prior to insertion, the distal end of the cannula positioned ator near the desired support location, and the pusher rod operated fromthe proximal end to push the support distally out of the distal end ofthe cannula and into the canal. The cannula and/or the pusher rod may beflexible and small enough in diameter to extend at least partiallyaround the canal. In some variations, a proximal end of a suture can beintroduced into the canal via a cannula and the suture extendedcircumferentially around the canal. A distal portion of the suture canbe connected to the support and force applied to the proximal end of thesuture to pull the support into the canal. The support can then bepositioned within the canal by pulling the suture in a distal orproximal direction. The suture can be used to anchor the support withinthe canal. In other variations, the support can be directly introducedinto the canal using surgical forceps, or the like.

FIGS. 14A-D illustrate additional variations for introducing a supportinto the canal. As shown in FIG. 14A, a support 200 can be introducedinto the canal using syringe 202 and plunger 204. Syringe 202 has distalend 206 that can be at least partially inserted into or placed adjacentto an opening in the canal. Force in a distal direction is applied toplunger 204, thereby pushing support 200 into the canal. Referring toFIGS. 14B-C, distal end 208 of guide element 210 can be at leastpartially introduced into the canal. Guide element 210 can be a guidewire. Guide element 210 can be extended circumferentially along thecanal to aid in positioning the support. Support 212 comprises centralbore 218 capable of accommodating guide element 210 such that support212 can be threaded onto guide element 210 and slidably positioned alongthe guide element. Once distal end 209 of support 212 is threaded ontoguide element 210, support 212 can be pushed in a distal direction alongguide element 210 to insert support 212 into the canal. In somevariations, support 212 can remain threaded onto guide element 210, andguide element 210 can remain in the canal. In other variations, support212 can be slid off distal end 208 of guide element 210, and the guideelement can be pulled in a proximal direction for removal. Referring toFIGS. 14C-D, syringe 202 with plunger 204 can be used in combinationwith a guide element 210. In this variation, distal end 208 of guideelement 210 is inserted at least partially into Schlemm's canal. Guideelement 210 can be extended circumferentially along the canal to aid inpositioning the support. Support 212 has central bore 218 capable ofaccommodating guide element 210. Proximal end 211 of guide element 210is inserted into bore 218. Plunger 204 is depressed in a distaldirection to push support 212 into the canal and slide support 212 alongelement 210. Guide element 210 can remain in the canal or be removedfollowing insertion of the support. Supports 200, 212 must besufficiently resilient to withstand force encountered as they are pushedinto the canal.

In some variations, a positioning device may be used with the introducerto position or adjust the support within the canal. A positioning devicecan include a rod, grippers, a clamp, a hook, or the like. In othervariations, a device or system capable of dilating the canal tofacilitate insertion of a support may be included in the kits, e.g., asyringe or other device capable of injecting fluid into the canal.

In some variations, the kits contain at least two supports. Multiplesupports can be implanted within one eye or within multiple eyes. If thekits contain multiple supports, the kits may also contain multipleintroducers. Alternatively, the same introducer may be used forimplantation of multiple supports, especially if the multiple supportsare being delivered to a single eye. If multiple supports are to bedelivered with the same introducer, then the multiple supports can bepreloaded into the introducer for sterility. If more than one support isincluded in a kit, the supports may be of different shapes, sizes,lengths, or materials. If the kits contain more than one support to beimplanted into a single eye, the supports can be connected together.

The kits can comprise an active agent, such as a pharmaceutical agent.The active agent may be included as an integral part of the support, ormay be supplied in kits for application to the support or to the eyeduring or after implantation. Examples of active agents that may besupplied as part of the kits include prostaglandins, prostaglandinanalogs, beta blockers, alpha-2 agonists, calcium channel blockers,carbonic anhydrase inhibitors, growth factors, such as tissue growthfactors or vascular endothelial growth factors, anti-metabolites,chemotherapeutic agents such as mitomycin-C,5-fluorouracil, steroids,antagonists of growth factors, such as antagonists of vascularendothelial growth factor, and combinations thereof.

The kits may contain a fixation device for attaching a support totissue. Such a fixation device can include sutures, hooks, barbs, clips,adhesives, and combinations thereof. In addition, the kits may include asystem for visually enhancing the support to facilitate viewing,positioning, and monitoring of a support. A system for visuallyenhancing the support can include a light source, a transmission orabsorption filter, a mirror, a composition comprising a chromophorecapable of fluorescing or phosphorescing that can be applied to thesupport, or any combination thereof. Chromophores can assist a clinicianin verifying the position of the support postoperatively using agonioscope, for example. The light source is capable of exciting achromophore contained within or on the support such that the chromophoreemits fluorescence or phosphorescence. The emission is preferably withinthe wavelength range of about 300 nm to about 800 nm. A suitable lightsource for such a system can comprise a laser, a light emitting diode,or a lamp. In some instances, transmission or absorption filters may beused to further select the wavelength range of the excitation source orview or detect emission from chromophores. One or more mirrors may beused to direct a light source or emitted light, or to view the support.

Methods

Methods for reducing intraocular pressure are also provided. In general,the methods comprise inserting a support circumferentially withinSchlemm's canal, such that the support maintains the patency of at leasta portion of the canal. The support occupies at least a portion of acentral core of Schlemm's canal and does not substantially interferewith transmural flow across Schlemm's canal.

The methods can comprise inserting a support circumferentially intoSchlemm's canal using an introducer and/or a positioning device. Theintroducer can include a cannula and a tubular or hollow pusher rod. Thesupport can be installed in the lumen of the cannula at its distal endand the pusher rod can be inserted into the lumen of the cannula at itsproximal end and extended distally to push the support into position inthe canal. In some instances, the cannula and/or the pusher rod may beflexible and small enough in diameter to at least partially extendcircumferentially around the canal. In some variations of the methods, apositioning device can be used in addition to an introducer. Thepositioning device can comprise a second rod, a gripper, a hook, aclamp, or the like. In some variations, the methods include illuminatinga support with a light source to causes the support to fluoresce orphosphoresce, thus aiding the visual appearance of the support. Theilluminating of the support can occur during or after implantation toinspect the support, e.g., to monitor its position, condition, orperformance.

In some instances, the methods will also comprise dilating Schlemm'scanal prior to insertion of the support. Dilation of the canal can beaccomplished by injecting fluid into the canal. For example, a highviscosity fluid such as sodium hyaluronate, or other dilating fluidsknown in the art, can be used to dilate the canal.

The methods may include implanting more than one support into an eye. Insome variations, the methods will include implantation of two or moresupports circumferentially adjacent to each other within the canal, andin other variations, the methods will include implantation of supportscircumferentially opposed to each other within the canal, e.g., twosupports centered about 180° apart around the circumference of Schlemm'scanal. Some variations of the methods can comprise connecting togethermultiple supports in a single eye.

In some variations, the methods can include anchoring the support totissue surrounding Schlemm's canal. Anchoring the support to tissue canbe accomplished in a variety of ways, e.g., by suturing, application ofadhesives, installation of hooks, clips, or the like, or combinationsthereof. In other variations, the methods can comprise selecting thesize of the support such that the support fits securely into the canalby a friction fit. Examples of arcuate supports that can be implantedwith a friction fit are illustrated in FIGS. 11A-C.

The methods described here can also include altering the support usingelectromagnetic radiation. For example, a support can include regionscapable of preferentially absorbing a certain wavelength range. Whenelectromagnetic radiation of the appropriate wavelength range withsufficient energy is incident upon the support, material in thepreferentially absorbing regions will melt or ablate, resulting inperforations or indentations in the support at those regions. Forexample, a pulsed titanium sapphire laser emitting at about 750 nm toabout 800 nm incident on gold can cause the gold to melt or ablate. Thealteration of the support using electromagnetic radiation can occurbefore or after implantation of a support. For example, fenestrationscan be created or enlarged in a support after the support has remainedin an eye for a period of time to enhance drainage.

While the inventive devices, kits and methods have been described insome detail by way of illustration, such illustration is for purposes ofclarity of understanding only. It will be readily apparent to those ofordinary skill in the art in light of the teachings herein that certainchanges and modifications may be made thereto without departing from thespirit and scope of the appended claims. For example, it is envisionedthat the devices, kits and methods can be applied to nonhuman eyes toreduce intraocular pressure, e.g., in dogs, cats, primates, or horses.

What we claim is:
 1. A method for treating a condition of the eye,comprising: delivering a high viscosity fluid into Schlemm's canal;inserting a distal end of an introducer into Schlemm's canal; andplacing a support in Schlemm's canal by operating the introducer.
 2. Themethod of claim 1, wherein the introducer comprises a pusher rod.
 3. Themethod of claim 2, wherein the support is advanced by operating thepusher rod from a proximal end of the introducer.
 4. The method of claim1, further comprising anchoring the support to tissue surroundingSchlemm's canal.
 5. The method of claim 1, further comprising using agonioscope.
 6. The method of claim 1, further comprising adjusting theposition of the support using a positioning device.
 7. The method ofclaim 1, wherein the support extends about a quarter or less than aquarter of the circumference of Schlemm's canal after placement.
 8. Themethod of claim 1, wherein at least a portion of the support extends outof Schlemm's canal after placement.
 9. The method of claim 1, whereinthe support does not substantially interfere with longitudinal flowalong the canal after placement.
 10. The method of claim 1, wherein thesupport enhances transmural flow across the wall of the canal afterplacement.
 11. The method of claim 1, wherein the support extendscircumferentially along Schlemm's canal after placement.
 12. The methodof claim 1, wherein when the support is disposed within a cylindricalsection of the lumen of Schlemm's canal having an internal wall surfacearea C, the support contacts less than 30% of C.
 13. The method of claim1, wherein when the support is disposed within a cylindrical section ofthe lumen of Schlemm's canal having an internal wall surface area C, thesupport contacts less than 10% of C.
 14. The method of claim 1, whereinthe high viscosity fluid is sodium hyaluronate.
 15. The method of claim1, wherein at least a portion of the support is made from a shape memorymaterial.
 16. The method of claim 15, wherein the shape memory materialcomprises a shape memory alloy.
 17. The method of claim 16, wherein theshape memory alloy comprises a nickel titanium alloy.
 18. The method ofclaim 1, wherein the support is flexible.
 19. The method of claim 1,wherein the support comprises a central bore.
 20. The method of claim 1,wherein the support comprises at least one fenestration.